Studies will continue on the structural basis for specific protein-nucleic acid interactions at the molecular level. The core of the experimental approach will continue to be the preparation of crystalline specimens and their analysis by X-ray diffraction. The crystallographic studies will be supplemented by chemical experiments (e.g., covalent cross-linking); spectral studies (e.g., NMR), and genetic studies (e.g., Km mutants) designed to indicate which regions of the nucleic acid or protein molecule mediates the interaction. The systems to be examined are as follows: (1) The three-dimensional structure determination of yeast tRNA F met will be completed to 5.7 A and extend to 4 A with a view towards discerning the structural basis of its unique role as the initiator of protein synthesis; (2) Proteins which form specific complexes with tRNA as well as the complexes themselves. Milligram quantities of tRNA-nucleotidyl transferase (crystalline), yeast met-RNA ligase, Salmonella his-tRNA ligase, and E. coli elongation factor, EF-Tu, are currently available in pure form in our laboratory throughout our isolation procedures (transferase and met ligase) or through collaboration (his ligase and EF-Tu), (3) TF1, a 12,000 M.W. protomer shown, in vitro, to selectively repress the transcription of SP01 phage DNA, has been crystallized in a form suitable for X-ray diffraction. BIBLIOGRAPHIC REFERENCES: R.W. Schevitz, N. Krishnamachari, J. Hughes, J. Rosa, M. Pasek, G. Cornick M.A. Navia and P.B. Sigler. The crystal structure of yeast tRNAFmet. A map of an initiator tRNA at 6 A resolution. In Structure and Conformation of Nucleic Acids and Protein-Nucleic Acid Interactions. M. Sundaralingam and S.T. Rao, Eds. University Park Press, Baltimore. pp. 85-99 (1975). P.B. Sigler. An analysis of the structure of tRNA. Ann. Rev. of Biophysics and Bioengineering. 477-527. Volume 4, 1975.